DESCRIPTION: (Applicant's Abstract) Major depression co-occurs commonly in the population of cocaine dependent patients. Despite high prevalence and negative consequences on illness course and prognosis, little is known about effective treatments for dual diagnosis. Traditional models treat each disorder separately, an approach that has proven ineffective. The proposed study provides a direct and logical extension of our previous research evaluating treatments that focus simultaneously on cocaine and mood disorders using integrated cognitive behavioral therapy (CBT) and antidepressant therapy. The study will employ a double-blind, placebo-controlled design in which depressed, cocaine-dependent patients will be randomized into one of four treatment conditions according to a full W factorial research design. Two levels of psychotherapy will compare integrated CBT and Clinical Management (CM) for depression and substance use. Two levels of pharmacotherapy will compare bupropion 400 mg/d and placebo. Dually-diagnosed subjects (N=140) will be treated for 12 weeks, then followed for 12 months. The design provides sufficient power to test both the independent and interactive effects of psychotherapy and pharmacotherapy. The integrated CBT is based on concepts and techniques shared by both Marlatt's Relapse Prevention model of substance abuse and Rehm's Self Control model of depression therapy. Data collected during the original funding period support the feasibility and potential utility of the integrated CBT approach and warrant progression to a larger-scale Stage II efficacy study. The CM approach adapted for this study will provide nonspecific elements of psychotherapy (e.g., support, education, empathy, and advice) and thus serve as an adequate psychotherapy-control condition. Our rationale for testing bupropion is based on its specific dopaminergic activity, efficacy as an antidepressant, low side-effect profile, and preliminary evidence of positive response in depressed cocaine-abusing patients. The study is technically rigorous, theoretically innovative, and scientifically significant. Careful screening and structured clinical interviewing will be used to collect information for making reliable and valid diagnostic judgments of cocaine dependence and current comorbid mood disorder based on DSM-IV criteria. Written therapy manuals, trained therapists, competency checks, and adherence rating scales will be used to verify treatment fidelity. Procedures to safeguard against adverse events will include initial medical evaluation, monitoring of medication plasma levels, daily recording of pill taking using an electronic medication dispensing unit, twice-weekly clinic visits, and regular contact with study psychiatrists. The assessment battery captures the domains of diagnoses, substance use patterns, mood symptomatology, addiction severity, and psychosocial functioning. Primary outcome measures will be cocaine use (via observed urine samples) and depression ratings (BDI, HDRS). Repeated assessments at 3-, 6-, 9-, and 12-months following treatment will be used to evaluate relapse rates, patterns, and predictors. This research will contribute important new theoretical and empirical information concerning efficacious treatment for cocaine dependent patients with comorbid mood disorders. Further, these studies will enhance our knowledge about the relation between dual disorders, the relative effects of treatment on mood and substance use outcomes, and the optimal combination of pharmacologic and psychotherapeutic treatments for this important subpopulation of patients.